In the field of treating bronchial diseases but also other diseases in which medication can be effected by way of the respiratory tract, it is known to apply medicaments in powder form, besides the atomisation of solutions or suspensions to afford inhalable aerosols. Many different examples of such medicaments are described in the literature, purely by way of example we refer to WO 93/11773, EP 0 416 950 A1 and EP 0 416 951 A1. A usual form of application in that respect is a supply by way of an inhalation device or inhaler.
In the case of inhalers for powder drugs, such inhalers are known both for the application of an individual dose, and also inhalation devices which have a store for a multiplicity of drug doses. In regard to the latter it is known either to provide separate storage chambers for a respective individual dose or an individual receiving chamber for accommodating a plurality of doses of a medicament.
In the case of inhalers which have a plurality of individual doses in separate storage chambers, those are known in which individual chambers of the inhaler are respectively filled with a drug dose. An example of such an inhaler is described in U.S. Pat. No. 5,301,666 A. It is however also known for a plurality of drug powder doses to be respectively separately disposed in the spaces or chambers of so-called blister packs. An example of such a blister pack for use with an inhaler is described in DE 44 00 083 C2. Such a blister pack which at the same time is in the form of a disposable inhaler is described for example in DE 44 00 084 A1.
An inhalation device into which blister packs can be fitted which include respective separate storage chambers for individual doses of a powder drug and which can be emptied successively by means of the inhalation device is described for example in DE 195 23 516 C1.
Many different examples of inhalers with a storage chamber for a plurality of drug doses are described in the state of the art. An example with a replaceable storage container is described in German patent specification 846 770, and another one is described in WO 95/31237.
A serious problem in inhalation systems in which a plurality of doses of a medically effective substance is disposed in a common storage chamber is apportioning an individual dose for an individual inhalation operation. A large number of proposed solutions have been set forth in that respect as described for example in U.S. Pat. Nos. 2,587,215 A and 4,274,403 A. Other forms of arrangements for dosing an individual drug powder dose from a storage chamber for a plurality of drug doses are also described in WO 92/09322, WO 93/16748, WO 93/03785, U.S. Pat. No. 6,029,661 A and DE 35 35 561 C2 as well as GB 2 165 159 A. An interchangeable cartridge for accommodating a plurality of doses of a drug powder with an integrated dosing slider is known from DE 195 22 415 A1.
A further serious problem in the inhalation of drug powder is the breakdown of the galenic powder formulations into particles which can reach the lungs. The active substances administered in that way are generally brought together with carrier substances in order to achieve reasonable dosability of the medically active substance and in order to set further properties of the drug powder which for example can involve storage capability.
Approaches involving the design configurations of powder inhalers which are intended to provide for the provision of particles which are capable of reaching the lungs in an air flow are described for example in EP 0 640 354 A2, U.S. Pat. Nos. 5,505,196 A, 5,320,714 A, 5,435,301 A, 5,301,666 A, DE 195 22 416 A1 and WO 97/00703. In that respect proposals are also known for using auxiliary energy for producing the airflow, for example from ZA-A 916741.
It is quite generally also known in regard to the use of medicaments for inhalation in powder form for active substances to be combined by the application of prefabricated active substance mixtures. Corresponding proposals are to be found in EP 0 416 951 A1 and WO 93/11773, for example for the combination of salmeterol with fluticasone or formoterol with budesonide.
WO 00/74754 and many other publications over more than twenty years describe that a serious problem arises in regard to moisture, particularly with powder inhalers. In that respect moisture can not only have a disadvantageous effect on the pharmaceutically active medicament composition but in particular can adversely affect the interplay of physical and chemical parameters of the combination of active substance and adjuvant substances. As a result for example lumps can occur or breakdown of the inhaled powder into particles capable of reaching the lungs can be impeded. All those circumstances can lead to problems in regard to dosability and the effectiveness of administration of a medicament powder.
To alleviate those disadvantages various attempts have already been made in the past to reduce the penetration of moisture into a powder inhaler by the use of seals. In addition attempts were made to reduce the detrimental effects of moisture which has penetrated into the inhaler, by the provision of drying agents in order to absorb the moisture and in particular to keep down the level of air humidity in the storage chambers. Sealed dosing cavities in a multi-dose powder inhaler as well as a multi-digit counting mechanism are known from WO 92/00771. It will be noted however that dosing is only described by way of a rotary movement of a frustoconical dosing member.
Measures for moisture protection of medicament in powder form for inhalation in respect of dosing by means of a dosing slider are described for example in DE 102 02 940 A1, US 2003 0136405 A and WO 03/061742 A2.